Deoxyhypusine synthase (DHPS) inhibitor GC7 induces p21/Rb-mediated inhibition of tumor cell growth and DHPS expression correlates with poor prognosis in neuroblastoma patients

PURPOSE: Neuroblastoma (NB) is an aggressive pediatric malignancy that typically occurs in infants and children under the age of 5 years. High-stage tumors relapse frequently even after aggressive multimodal treatment, resulting in therapy resistance and eventually in patient death. Clearly, new biologically-targeted drugs are needed that more efficiently suppress tumor growth and prevent relapse. We and others previously showed that polyamines such as spermidine play an essential role in NB tumorigenesis and that DFMO, an inhibitor of the central polyamine synthesis gene ODC, is effective in vitro and in vivo, prompting its evaluation in NB clinical trials. However, the specific molecular actions of polyamines remain poorly defined. Spermidine and deoxyhypusine synthase (DHPS) are essential components in the hypusination-driven post-translational activation of eukaryotic initiation factor 5A (eIF5A). METHODS: We assessed the role of DHPS in NB and the impact of its inhibition by N(1)-guanyl-1,7-diaminoheptane (GC7) on tumor cell growth using cell proliferation assays, Western blot, immunofluorescence microscopy, and Affymetrix micro-array mRNA expression analyses in NB tumor samples. RESULTS: We found that GC7 inhibits NB cell proliferation in a dose-dependent manner, through induction of the cell cycle inhibitor p21 and reduction of total and phosphorylated Rb proteins. Strikingly, high DHPS mRNA expression correlated significantly with unfavorable clinical parameters, including poor patient survival, in a cohort of 88 NB tumors (all P < 0.04). CONCLUSIONS: These results suggest that spermidine and DHPS are key contributing factors in NB tumor proliferation through regulation of the p21/Rb signaling axis

Microbiological assessment of raw goat milk collected from Sardinian herds

With Regulation EC 853/04, the European Parliament and the Council laid down general rules for food business operators regarding the hygiene of foodstuffs. In particular, the regulation established ≤1.500.000 cfu/mL as the maximum-tolerated value for total bacterial count in raw goat milk. Moreover, in order to enhance the hygiene of dairy farms, the Sardinia Region has funded the <em>F measure</em> programme which provides rewards for farmers showing improvements in herd management and animal welfare practices. This work aimed to evaluate the microbiological quality of raw goat milk samples collected during the F measure enforcement. A total of 536 raw goat samples, collected from dairy farms in the Sardinian province of Nuoro and Ogliastra, were analised for total bacterial count at 30°C. Results showed that total bacterial count was ≤1.500.000 ufc/mL in 456 (85.1%) raw milk goat samples, most of them (80.2%) with a total bacterial contamination &lt;500.000 cfu/mL. This study confirms the hygienic good quality of raw goat milk collected from Sardinian dairy farms

Characterization and the impact of in vitro simulated digestion on the stability and bioaccessibility of carotenoids and their esters in two Pouteria lucuma varieties

Lucuma is a starchy orange-yellow fruit native to the Andean region. It is widely consumed in Latin America and has been recently adapted to the agronomical characteristics of the south region of Spain. However, its carotenoid profile has never been reported. The aim of this study was to characterize the carotenoid and carotenoid ester composition of lucuma pulps (var. Molina and Beltran) and assess their bioaccessibility with an in vitro simulated gastrointestinal digestion according to the INFOGEST® methodology. The carotenoid profile in lucuma pulps revealed a high qualitative diversity composed of 33 compounds, corresponding to 9 free xanthophylls, 9 hydrocarbon carotenes and 15 xanthophyll esters. (13Z)-violaxanthin, (all-E)-violaxanthin and (all-E)-antheraxanthin were the most abundant carotenoids in lucuma fruits and were naturally present as xanthophyll esters: (all-E)-antheraxanthin 3-O-palmitate, (all-E)-violaxanthin laurate and (all-E)-violaxanthin palmitate. Carotenoids were stable during in vitro digestion; however, their release from the food matrix was limited which contributed to their low bioaccessibility.The authors would like to express gratitude for the funding received from Spanish Ministry of Science and Innovation (project INIA RTA2015-00044-C02-02) of Spanish Government. We thank the Institute for Mediterranean and Subtropical Horticulture “La Mayora” (IHSM-UMA-CSIC) in Malaga (Spain) for the lucuma fruits. Author Andrea Gómez-Maqueo thanks CONACyT, Mexico, for her doctoral scholarship, no. 692751. Author Elisa Bandino thanks ERASMUS + for her master’s scholarship KA1 no. 103.Peer reviewe